Treatment with hydroxyurea and tyrphostin-1 significantly improves the transduction efficiency of recombinant adeno-associated viruses in human cancer cells

Sung Jin Kim, Young Ran Nam, Ohkyu Shin, Jene Choi, Boyoung Lee, JinWoo Chang, Yunhee Kim Kwon, Keerang Park, Heuiran Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

To enhance the transduction efficiency (TE) of a recombinant adeno-associated virus 2 (rAAV2) in human cancer cells, we examined the combined effects of various chemicals known to influence the rAAV2 transduction process at distinct steps. Among the agents tested were trichostatin A, a histone deacetylase inhibitor, MG-132, a proteosome inhibitor, the genotoxic agents hydroxyurea, aphidicolin, etoposide and camptothecin, and tyrphostin-1, an epidermal growth factor receptor inhibitor. During or after chemical treatment, various human cancer cells were infected with rAAV2 expressing β-galactosidase. Treatment with hydroxyurea or etoposide plus tyrphostin-1 dramatically increased the TE in most cell lines. The combination of hydroxyurea plus tyrphostin-1 increased TE to 37.7±7.9%, 32.8±2.0% and 31.8±2.1% in SK-Hepl, HeLa, and HCT116 cells, respectively. In addition, following rAAV2 infection and treatment with hydroxyurea plus tyrphostin-1, long-term transgene expression was observed for up to 6 months, with no damage to the transduced cells. These results indicate that rAAV2 transgene expression can be significantly enhanced by a combination of chemical agents with distinct activity and prolonged gene expression can occur following rAAV2 gene transfer into human cancer cells.

Original languageEnglish
Pages (from-to)1475-1479
Number of pages5
JournalOncology Reports
Volume14
Issue number6
Publication statusPublished - 2005 Dec 1

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Tyrphostins
Dependovirus
Hydroxyurea
Neoplasms
Etoposide
Transgenes
trichostatin A
Galactosidases
Aphidicolin
HCT116 Cells
Camptothecin
Histone Deacetylase Inhibitors
Virus Diseases
HeLa Cells
Epidermal Growth Factor Receptor
Gene Expression
Cell Line
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, Sung Jin ; Nam, Young Ran ; Shin, Ohkyu ; Choi, Jene ; Lee, Boyoung ; Chang, JinWoo ; Kwon, Yunhee Kim ; Park, Keerang ; Lee, Heuiran. / Treatment with hydroxyurea and tyrphostin-1 significantly improves the transduction efficiency of recombinant adeno-associated viruses in human cancer cells. In: Oncology Reports. 2005 ; Vol. 14, No. 6. pp. 1475-1479.
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abstract = "To enhance the transduction efficiency (TE) of a recombinant adeno-associated virus 2 (rAAV2) in human cancer cells, we examined the combined effects of various chemicals known to influence the rAAV2 transduction process at distinct steps. Among the agents tested were trichostatin A, a histone deacetylase inhibitor, MG-132, a proteosome inhibitor, the genotoxic agents hydroxyurea, aphidicolin, etoposide and camptothecin, and tyrphostin-1, an epidermal growth factor receptor inhibitor. During or after chemical treatment, various human cancer cells were infected with rAAV2 expressing β-galactosidase. Treatment with hydroxyurea or etoposide plus tyrphostin-1 dramatically increased the TE in most cell lines. The combination of hydroxyurea plus tyrphostin-1 increased TE to 37.7±7.9{\%}, 32.8±2.0{\%} and 31.8±2.1{\%} in SK-Hepl, HeLa, and HCT116 cells, respectively. In addition, following rAAV2 infection and treatment with hydroxyurea plus tyrphostin-1, long-term transgene expression was observed for up to 6 months, with no damage to the transduced cells. These results indicate that rAAV2 transgene expression can be significantly enhanced by a combination of chemical agents with distinct activity and prolonged gene expression can occur following rAAV2 gene transfer into human cancer cells.",
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Treatment with hydroxyurea and tyrphostin-1 significantly improves the transduction efficiency of recombinant adeno-associated viruses in human cancer cells. / Kim, Sung Jin; Nam, Young Ran; Shin, Ohkyu; Choi, Jene; Lee, Boyoung; Chang, JinWoo; Kwon, Yunhee Kim; Park, Keerang; Lee, Heuiran.

In: Oncology Reports, Vol. 14, No. 6, 01.12.2005, p. 1475-1479.

Research output: Contribution to journalArticle

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